Offspring exposed to maternal diabetes during pregnancy had more than twice the risk of developing multiple sclerosis in adulthood, while birth weight for gestational age showed opposing associations with risk, according to a large population-based cohort study conducted in Norway.

In a nationwide analysis of more than 1 million births, researchers evaluated whether adverse pregnancy outcomes and fetal growth characteristics were associated with the long-term risk of multiple sclerosis (MS). Preterm birth, maternal hypertensive disorders of pregnancy, and placental abruption were not associated with MS risk, whereas fetal growth extremes and maternal diabetes were associated with altered risk.

Researchers analyzed linked data from Norwegian national registries including the Medical Birth Registry of Norway and the Norwegian Patient Registry. The cohort included 1,303,802 live births between 1967 and 1989. After excluding patients who had died or emigrated before follow-up, those with missing or implausible birth data, and those exposed to maternal type 1 diabetes, the analytic sample comprised 1,166,731 patients. Follow-up for incident MS began in January 2009, when patients were at least 18 years old and MS-free in the prior year and continued through December 2019. MS diagnoses were identified using International Classification of Diseases, Tenth Revision, code G35, which has a validated positive predictive value of 92%.

Exposures of interest included preterm birth before 37 completed weeks; birth weight for gestational age categorized as small for gestational age, appropriate for gestational age, or large for gestational age; maternal hypertensive disorders of pregnancy; placental abruption; and maternal diabetes, defined as gestational diabetes, type 2 diabetes, unspecified pregestational diabetes, or use of antidiabetic medication during pregnancy. Cox proportional hazards models used age as the timescale and were adjusted for sex, birth cohort, maternal age at delivery, parity, plurality, maternal education, and maternal country of origin, with additional adjustments for co-occurring pregnancy complications as appropriate.

During nearly 14.9 million person-years of follow-up, 4,295 MS cases were identified. Compared with appropriate-for-gestational-age births, large-for-gestational-age births were associated with a 13% higher MS risk, while small-for-gestational-age births were associated with a 12% lower risk. Exposure to maternal diabetes was associated with more than a twofold increased risk of MS. “While it is well established that children with high BMI and diabetes are more likely to develop MS in adulthood, our findings suggest that the roots may lie in the perinatal period,” wrote lead author Katrin Wolfova, PhD, of the Department of Neurology at Columbia University, and colleagues.

There were several limitations. Adverse pregnancy outcomes, particularly maternal diabetes, may have been underreported in registry data, and the study could not adjust for maternal obesity, smoking, or vitamin D status. Gestational age was based on last menstrual period rather than ultrasonography, and changes in obstetric and MS diagnostic practices over time may have introduced nondifferential misclassification. In addition, fetal growth patterns in Norway differ from international reference populations, which may limit generalizability.

Full disclosures can be found in the published study.

Source: JAMA Neurology